In a joint study with investigators in Laboratory of Molecular Biology, NCI and Institut National de la Recherche Agronomique (INRA), France, we are attacking the problem of protein structure classification, with the goal of improving automated methods for recognition and classification of protein domains in three dimensional structures. Domains are thought to be the building blocks of complex structures, and often determine protein function. We have recently shown that two distinct structure similarity measures (VAST and SHEBA) can obtain at best about 75-80% agreement with a standard manually curated protein classification (SCOP), calling into question the existence of sharp boundaries between protein "folds". We have published a further analysis of "C-class" or alpha/beta protein domains, by hierarchically clustering domains based on measured structural similarity by three different methods (VAST, SHEBA and DALI). We found that automatic classifications differ little from each other, relative to their overall differences from SCOP. One implication is that identification of conserved motifs or cores may be necessary before identifying domain classes. We are now developing and testing novel algorithms for domain definition within the structure of multidomain proteins.[unreadable] [unreadable] With an investigator in the Division of International Epidemiology and Population Studies, Fogarty International Center, we have developed a phenomenological model of Plasmodium/red blood cell dynamics moderated by host immune and erythropoietic responses. We have found that the tight synchronization of the asexual reproductive cycle of the parasites seen clinically may actually be beneficial to host by limiting parasitemia and severity of anemia. A report describing the results of this work was published in PLoS Computational Biology. We are studying how regulation of parasitmia by both host and parasite factors affects transmissibility of the parasite to its mosquito vector.[unreadable] [unreadable] [unreadable] Working with experimental investigators in the Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, we are studying the population biology of Plasmodium parasites within their mosquito vectors. [unreadable] [unreadable] [unreadable] With investigators in the Section on Medical Biophysics, Laboratory of Integrative Biophysics, National Institute of Child Health and Human Development, and with the Signal Processing and Instrumentation Section, Computational Bioscience and Engineering Laboratory, Division of Computational Bioscience, Center for Information Technology, we are working of a model of the thermal and fluid transport processes that occur in the operation of expression microdissection (xMD), a newly developed method of extraction large number of cells from a tissue sample. xMD shows great promise, but a better theoretical understanding of its operations is needed before it can commercially developed or be fully exploited in an NIH core facility.[unreadable] [unreadable] With investigators in NIMH, we analyzed multiple-electrode recordings from in-vitro neural network preparations in order to deduce the underlying cortical network topology. We found that such functional networks show a strong "small world" property, meaning high clustering among the nodes and short node-to-node distances. More importantly, we found a novel property of these networks when the weights of the network links are taken into account. Simulations indicate that such network architecture results when the link weights are correlated with the clustering coefficients of the respective end nodes. [unreadable] [unreadable] In a project with investigators of NIMH (Dietmar Plenz), we developed a new algorithm for network reconstruction from the observed avalanche dynamics in multiple electrode neuronal recordings. This work has been submitted PLoS Computational Biology, in July 2008, and is currently being revised. Applying this algorithm to the multiple-electrode recordings from in-vitro neural network preparations we revealed a novel property of these networks which show robust clustering properties upon removal of the weak links. Simulations indicate that such network architecture results when the link weights are correlated with the clustering coefficients of the respective end nodes. A manuscript describing this work is in preparation.[unreadable] [unreadable] In a new project with investigators in the Laboratory of Integrative and Medical Biophysics (LIMB), NICHD (Peter J. Basser) we made a theoretical study of the observed skewed and heavy-tailed distribution of the axonal diameters. We show that the observed distribution can arise when optimizing the information transfer through axonal bundles. This work will be presented at the Annual Meeting of the Society for Neuroscience in Washington D.C. in November, 2008. In collaboration with the same group, previously described approximation scheme for diffusion tensors has been extended to accept a general vector field and implemented in C and Matlab, to be used in the new projects.[unreadable] [unreadable] In another project with LIMB, NICHD (Victor Chernomordik and Amir Gandjbakche) and MSCL/DCB/CIT (George H. Weiss), related to the development of the optical imaging techniques we derived theoretical predictions for the effects of the photon-fluorophore interactions in the time-gated optical imaging techniques. A manuscript describing this work is also in preparation.